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Repurposing drugs with specific activity against L-form bacteria

Lookup NU author(s): Dr Kaveh Emami, Dr Ling Juan WuORCiD, Professor Jeff Errington

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

Copyright © 2023 Emami, Banks, Wu and Errington.Cell wall deficient “L- form” bacteria are of growing medical interest as a possible source of recurrent or persistent infection, largely because of their complete resistance to cell wall active antibiotics such as β-lactams. Antibiotics that specifically kill L-forms would be of potential interest as therapeutics, but also as reagents with which to explore the role of L-forms in models of recurrent infection. To look for specific anti-L-form antibiotics, we screened a library of several hundred FDA-approved drugs and identified compounds highly selective for L-form killing. Among the compounds identified were representatives of two different classes of calcium channel blockers: dihydropyridines, e.g., manidipine; and diphenylmethylpiperazine, e.g., flunarizine. Mode of action studies suggested that both classes of compound work by decreasing membrane fluidity. This leads to a previously recognized phenotype of L-forms in which the cells can continue to enlarge but fail to divide. We identified a considerable degree of variation in the activity of different representatives of the two classes of compounds, suggesting that it may be possible to modify them for use as drugs for L-form-dependent infections.

Publication metadata

Author(s): Emami K, Banks P, Wu LJ, Errington J

Publication type: Article

Publication status: Published

Journal: Frontiers in Microbiology

Year: 2023

Volume: 14

Online publication date: 04/04/2023

Acceptance date: 14/03/2023

Date deposited: 15/05/2023

ISSN (electronic): 1664-302X

Publisher: Frontiers Media S.A.

URL: https://doi.org/10.3389/fmicb.2023.1097413

DOI: 10.3389/fmicb.2023.1097413

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